Dimethylformamide → HCID 71452129, compound

Participants

Reaction Conditions

Reaction Steps

In a 20 mL vial, [5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-phenyl-ethyl ester (Example 1, 110.3 mg, 275 μmol), N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide (112 mg, 307 μmol), DPPF (38 mg, 68.5 μmol) and PdCl2(dppf)CH2Cl2 (39 mg, 47.8 μmol) were combined with DMF (5 mL) and the mixture was bubbled with nitrogen for 20 minutes to give a light brown/red solution. To this was added 2N Na2CO3 (550 μL, 1.1 mmol, degassed with nitrogen bubbled through for 20 min), and the red mixture (looked like salt precipitated) had nitrogen bubbled through for 1 min. The vial was sealed, placed in a dry block, and heated at 80° C. for 4 hr. The reaction was diluted with ethyl acetate (75 mL) and 0.1 M HCl (100 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (75 mL). The organic layers were washed with brine, dried over MgSO4, filtered, concentrated, and dried from DCM/hexanes to give a crude material (311 mg). The crude material was dissolved in minimal DCM and purified by flash chromatography (silica gel, 24 g Redisep, 30 mL/min, 0% to 100% EtOAc in hexanes, 0.5% AcOH). Appropriate fractions were combined, concentrated, dried from DCM/hexanes and DCM to yield {5-[4′-(1-methanesulfonylaminocarbonyl-cyclopropyl)-biphenyl-4-yl]-3-methyl-3H-[1,2,3]triazol-4-yl}-carbamic acid (R)-1-phenyl-ethyl ester (98.5 mg, 64% yield). LC/MS calcd. for C29H29N5O5S (m/e) 559, obsd. 560 (M+H, ES+). 1H NMR (DMSO-d6) δ ppm 11.16 (br. s., 1H), 9.93 (br. s., 1H), 7.80 (d, J=7.8 Hz, 2H), 7.62-7.76 (m, 4H), 7.06-7.57 (m, 7H), 5.65-5.93 (m, 1H), 3.85 (s, 3H), 3.20 (s, 3H), 1.38-1.76 (m, 5H), 1.20 (br. s., 2H).

Provenance & Evidence